Curcumin-loaded soluplus® based ternary solid dispersions with enhanced solubility, dissolution and antibacterial, antioxidant, anti-inflammatory activities.

Amorphous solid dispersion (ASD) has emerged to be an outstanding strategy among multiple options available for improving solubility and consequently biological activity. Interestingly several binary SD systems continue to exhibit insufficient solubility over time. Therefore, the goal of current research was to design ternary amorphous solid dispersions (ASDs) of hydrophobic model drug curcumin (CUR) to enhance the solubility and dissolution rate in turn, presenting enhanced anti-bacterial, antioxidant and anti-inflammatory activity. For this purpose several ternary solid dispersions (TSDs) consisting of Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) were prepared using solvent evaporation method. Both solubility and dissolution testing of prepared solid dispersion were performed to determine the increase in solubility and dissolution. Solid state investigation was carried out utilizing infrared spectroscopy, also known as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),Differential scanning calorimetry (DSC) and X-ray diffraction (XRD).Optimized formulations were also tested for their biological effectiveness including anti-bacterial, anti-oxidant and anti-inflammatory activity. Amid all Ternary formulations F3 entailing 20 % soluplus® remarkably improved the solubility (186 µg/ml ± 3.95) and consequently dissolution (91 % ± 3.89 %) of curcumin by 3100 and 9 fold respectively. These finding were also supported by FTIR, SEM, XRD and DSC. In-vitro antibacterial investigation of F3 also demonstrated significant improvement in antibacterial activity against both gram positive (Staphylococcus aureus, Bacillus cereus) and gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria. Among all the tested strains Staphylococcus aureus was found to be most susceptible with a zone of inhibition of 24 mm ± 2.87. Antioxidant activity of F3 was also notably enhanced (93 % ± 5.30) in contrast to CUR (69 % ± 4.79). In vitro anti-inflammatory assessment also exhibited that F3 markedly protected BSA (bovine serum albumin) from denaturation with percent BSA inhibition of 80 % ± 3.16 in comparison to CUR (49 % ± 2.91). Hence, F3 could be an effective solid dispersion system for the delivery of model hydrophobic drug curcumin.

Bile acid/fatty acid integrated nanoemulsomes for nonalcoholic fatty liver targeted lovastatin delivery: stability, in-vitro, ex-vivo, and in-vivo analyses.

BACKGROUND: Controlled and targeted drug delivery to treat nonalcoholic fatty liver disease (NAFLD) can benefit from additive attributes of natural formulation ingredients incorporated into the drug delivery vehicles. METHODS: Lovastatin (LVN) loaded, bile acid (BA) and fatty acid (FA) integrated nanoemulsomes (NES) were formulated by thin layer hydration technique for synergistic and targeted delivery of LVN to treat NAFLD. Organic phase NES was comprised of stearic acid with garlic (GL) and ginger (GR) oils, separately. Ursodeoxycholic acid and linoleic acid were individually incorporated as targeting moieties. RESULTS: Stability studies over 90 days showed average NES particle size, surface charge, polydispersity index, and entrapment efficiency values of 270 ± 27.4 nm, -23.8 ± 3.5 mV, 0.2 ± 0.04 and 81.36 ± 3.4%, respectively. Spherical NES were observed under a transmission electron microscope. In-vitro LVN release depicted non-fickian release mechanisms from GL and GR oils-based NES. Ex-vivo permeation of BA/FA integrated NES through isolated rat intestines showed greater flux than non-integrated ones. CONCLUSION: Liver histopathology of experimental rats together with in-vivo lipid profiles and liver function tests illustrated that these NES possess the clinical potential to be promising drug carriers for NAFLD.

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen.

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

Curcumin Encapsulation in Geranium Oil Microemulsion Elevates Its Antibacterial, Antioxidant, Anti-Inflammatory, and Anticancer Activities.

One of the major challenges with curcumin is its poor solubility in water, which limits its absorption and bioavailability in the body. This study aimed to develop and characterize stable microemulsions (MEs) as MEs increase the dispersibility of curcumin in water and aid its absorption in the body. Curcumin-loaded MEs were developed with the goal of enhancing topical delivery and its pharmacological activity (antioxidant, antibacterial, anticancer activity, and anti-inflammatory). The pseudoternary phase diagram was constructed to find out the desired microemulsion region. The prepared MEs (ME1-ME5) were evaluated for pH, viscosity, size of the particle, electrical conductivity, zeta potential, and ex vivo permeation of the drug. The optimized ME formulation was selected based on particle size and was further evaluated for biological activity (in vitro/vivo). In vitro cytotoxic effects of formulations were checked on the human liver cancer cell line, HEPG2 (a cell line exhibiting epithelial-like morphology that was isolated from a hepatocellular carcinoma). Geranium oil, Tween 80 (as a surfactant), and propylene glycol (as a cosurfactant) were screened out based on solubility to formulate MEs. The optimized ME formulation (ME5), with a composition of 20:50:30 (geranium oil:Tween 80:propylene glycol), exhibited pH 4.36 ± 0.057, conductivity of 40.06 ± 0.05 µS/cm, viscosity of 165 ± 0.37 mPa·s, and droplet diameter of 199.39 ± 0.017 nm. The ex vivo permeation study demonstrated a significant cumulative amount of curcumin permeated in 24 h and had a flux of 130.91 ± 0.02 µg/cm2/h. Antioxidant activity demonstrated that curcumin-loaded microemulsion (ME5) exhibited higher scavenging activity (99.27 ± 0.021%) than blank microemulsion (94.67 ± 0.001%). Optimized curcumin-loaded microemulsion (ME5) exhibited zones of inhibition of 25.18 and 28.37 mm against Escherichia coli and Staphylococcus aureus, respectively. Among the cell lines tested, a higher concentration of ME5 showed the greatest cytotoxicity with a % viability of 8.22 ± 1.09%. Evidently, it also revealed significant in vivo anti-inflammatory effects with 93.29 ± 0.030% inhibition by the carrageenan-induced paw edema model (6 h study) and 88.39 ± 0.002% inhibition by the formalin-induced paw edema model (14 day study). In conclusion, microemulsion was safe and effective for effective delivery of curcumin with the potential for antioxidant, antibacterial, cytotoxic, and in vivo anti-inflammatory activities.